1. Field of the Invention
The present invention relates to prostaglandin I.sub.2 (PGI.sub.2) derivatives.
2. Description of the Prior Art
Prostaglandin I.sub.2 (PGI.sub.2, also called prostacyclin) represented by the formula: ##STR2## was first found by J. R. Vane et al. in 1976. PGI.sub.2 is biosynthesized from arachidonic acid via endoperoxide (PGH.sub.2 or PGG.sub.2) in the vascular wall. It should be nloted that PGI.sub.2 shows potent platelet aggregation-inhibiting and gastric acid secretion-inhibiting activities and a potent peripheral blood vessel-dilating activity: refer to C & EN, Dec. 20, 1976, page 17; and S. Moncada, R. Gryglewski, S. Bunting and J. R. Vane, Nature, 263, 633 (1976).
PGI.sub.2 is extremely unstable even in neutral aqueous solutions due to its unstable exo-enol structure and readily converted into 6-oxo PGF.sub.1.alpha. which is substantially inactive physiologically. Such instability of PGI.sub.2 is a great obstacle to its use as a drug. Furthermore, PGI.sub.2 is unstable in vivo as well and disadvantageously shows only short duration of physiological activities in vivo.
Many studies have been made on various derivatives for the purpose of improving the chemical stability and duration of activities in vivo of PGI.sub.2.
The present inventors have also studied and solved this problem of chemical instability of PGI.sub.2 by providing novel derivatives of PGI.sub.2 having a cyclopenta[b]benzofuran ring in which the exo-enol structure contributing to the instability is incorporated into the phenyl ring. Thus, the present inventors have attained a series of inventions relating to such PGI.sub.2 derivatives and filed a number of patent applications: refer to Japanese Patent Application Laying-open (KOKAI) Nos. 56-36477, 57-32277, 57-144276, 58-124778 and 59-134787.
However, although the problem of chemical instability could be solved by the derivatives of PGI.sub.2 provided by these prior inventions, the potency of pharmacological activities and in vivo duration thereof are still unsatisfactory.
Accordingly, it is a primary object of this invention to solve such a problem.